Association between dopamine transporter (DAT1) genotype, left-sided inattention, and an enhanced response to methylphenidate in attention deficit hyperactivity disorder (ADHD)

Abstract

A polymorphism of the dopamine transporter gene (DAT1, 10-repeat) is associated with ADHD and has been linked to an enhanced response to methylphenidate (MPH). One aspect of the attention deficit in ADHD includes a subtle inattention to left space, resembling that seen after right cerebral hemisphere damage. Since left-sided inattention in ADHD may resolve when treated with MPH, we asked whether leftsided inattention in ADHD was related to DAT1 genotype and the therapeutic efficacy of MPH. Forty-three ADHD children and their parents were genotyped for the DAT1 3? VNTR polymorphism. The children performed the Landmark Test, a well-validated measure yielding a spatial attentional asymmetry index (leftward to rightward attentional bias). Parents rated their child?s response to MPH retrospectively using a three-point scale (No, Mediocre or Very Good Response). Additionally, parents used a symptom checklist to rate behaviour while on and off medication. A within family control design determined whether asymmetry indices predicted biased transmission of 10-repeat parental DAT1 alleles and/or response to methylphenidate. It was found that left-sided inattention predicted transmission of the 10-repeat allele from parents to probands and was associated with the severity of ADHD symptomatology. Children rated as achieving a very good response to MPH displayed left-sided inattention, while those rated as achieving a poorer response did not. Our results suggest a sub-group of children with ADHD for whom the 10-repeat DAT1 allele is associated with left-sided inattention. MPH may be most efficacious in this group because it ameliorates a DAT1-mediated hypodopaminergic state.